Study of CBP501/Cisplatin/Nivolumab Combinations in Advanced Pancreatic Cancer

Brief summary public domain (ClinicalTrials.gov)

Multicenter, randomized, open-label, parallel group phase 2 study to assess the efficacy and tolerance of four combinations of CBP501, cisplatin, and nivolumab administered once every 21 days to patients with stage IV exocrine pancreatic cancer and WBC \< 10,000/mm3 at screening.

Detailed description public domain (ClinicalTrials.gov)

Multicenter, randomized, open-label, parallel group phase 2 study to assess the efficacy and tolerance of four combinations of CBP501, cisplatin, and nivolumab administered once every 21 days to patients with stage IV exocrine pancreatic cancer and WBC \< 10,000/mm3 at screening. Patients will be randomized 1:1:1:1 to the following four treatment groups, with randomization stratified by ECOG PS (0 vs 1) and liver metastasis (present vs absent): 1. CBP501 25 mg/m2 + cisplatin 60 mg/m2 + nivolumab 240 mg 2. CBP501 16 mg/m2 + cisplatin 60 mg/m2 + nivolumab 240 mg 3. CBP501 25 mg/m2 + cisplatin 60 mg/m2 4. Cisplatin 60 mg/m2 + nivolumab 240 mg No more than 4 cycles of combination therapy may be administered but patients who remain progression-free after 4 cycles may receive up to 6 additional cycle of single-agent nivolumab. A Fleming two-stage design will be used. For each study arm, the null hypothesis that the true percentage of patients progression-free at 3 months is 10% will be tested against a one-sided alternative. In the first stage, 9 patients will be accrued to each study arm. In the first stage, if there are 1 or fewer patient progression-free at 3 months the study will be stopped for futility and if there are 4 or more patients progression-free at 3 months the study will stopped and the null hypothesis rejected. Otherwise, 14 additional patients will be accrued to the study arm for a total of 23. The null hypothesis will be rejected if 6 or more of 23 patients are progression-free at 3 months. This design yields a type I error rate of 2.5% and power of 80% when the true percentage of patients progression-free at 3 months is 35%.

Intervention public domain (ClinicalTrials.gov)

Drug: CBP501 (16). 16 mg/m2

Intervention public domain (ClinicalTrials.gov)

Drug: CBP501 (25). 25 mg/m2

Intervention public domain (ClinicalTrials.gov)

Drug: Cisplatin. 60mg/m2

Intervention public domain (ClinicalTrials.gov)

Drug: Nivolumab. 240 mg

Arm public domain (ClinicalTrials.gov)

Arm 1: CBP501 (25) + Cisplatin + Nivolumab (experimental): CBP501 25mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously. Nivolumab 240mg will be administered following the completion of CBP501 and cisplatin infusions.

Arm public domain (ClinicalTrials.gov)

Arm 2: CBP501 (16) + Cisplatin + Nivolumab (experimental): CBP501 16mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously. Nivolumab 240mg will be administered following the completion of CBP501 and cisplatin infusions.

Arm public domain (ClinicalTrials.gov)

Arm 3: CBP501 (25) + Cisplatin (experimental): CBP501 25mg/m2 and Cisplatin 60mg/m2 will be administered simultaneously.

Arm public domain (ClinicalTrials.gov)

Arm 4: Cisplatin + Nivolumab (experimental): Cisplatin 60mg/m2 will be administered as infusion and then Nivolumab 240mg will be administered.

Primary outcome public domain (ClinicalTrials.gov)

Three-month progression free survival rate (3M PFSR). Tumor assessment by RECIST v.1.1 criteria will be performed at screening, every 8 weeks starting after Cycle 1 Day 1, at the End-of-Treatment visit, and every 3 months after the End-of-Treatment visit until disease progression is observed. Time frame: 3 months after treatment.

Secondary outcome public domain (ClinicalTrials.gov)

Safety profiles of the combinations of CBP501, cisplatin, and nivolumab administered once every 21 days. Time frame: One year.

Secondary outcome public domain (ClinicalTrials.gov)

Progression-free survival (PFS). Time frame: one year.

Secondary outcome public domain (ClinicalTrials.gov)

Confirmed and timepoint objective response rates (cORR/ORR). Time frame: one year.

Secondary outcome public domain (ClinicalTrials.gov)

Duration of responses (DoR). Time frame: one year.

Secondary outcome public domain (ClinicalTrials.gov)

disease control rate (DCR: CR + PR + SD ≥12 weeks). Time frame: one year.

Secondary outcome public domain (ClinicalTrials.gov)

Overall survival (OS). Time frame: one year.

Eligibility public domain (ClinicalTrials.gov)

Inclusion Criteria: 1. Signed informed consent obtained prior to initiation of any study-specific procedures and treatment; 2. Patients with pathologically confirmed stage IV exocrine pancreatic cancer who have received at least two lines of systemic therapy for metastatic disease. Up to 10 of prior lines of systemic therapy (including prior cisplatin), chemoradiotherapy, radiotherapy or investigational agents the patient has received are allowed in order to be eligible, as long as all eligibility criteria are met, with the exception that a patient must not have received more than two prior lines incorporating anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune checkpoint blockade. Patients who have received prior anti-PD-1, anti-PD-L1, or anti-CTLA-4 immune checkpoint blockade therapy must have tolerated therapy with no evidence of grade 4 toxicity or an immune-related event (any grade) that required treatment discontinuation. Patients who experienced an endocrine related dysfunction are eligible, provided they are on stable hormone replacement therapy; 3. Male or female patients aged ≥ 18 years at time of informed consent; 4. ECOG Performance Status (PS) 0-1; 5. Life expectancy \> 3 months; 6. Previous anticancer treatment must be discontinued at least 3 weeks prior to the initiation of study treatment (with the exception of 6 weeks for mitomycin C; 6 weeks for anti-androgen therapy if discontinued prior to treatment initiation, and 8 weeks for bicalutamide); 7. Adequate bone marrow reserve, cardiac, liver, renal and metabolic function: * white blood cell count (WBC) \<10,000/mm3; * absolute neutrophil count (ANC) ≥ 1,500/mm3; * platelet count ≥ 100,000/mm3; * hemoglobin ≥ 9 g/dL; * creatinine phosphokinase isozymes CPK-MB and CPK-MM ≤ upper limit of normal (ULN); * serum troponin T levels within normal limits; * bilirubin ≤ 1.5 x ULN; * alanine aminotransferase (ALT, SGPT) and aspartate aminotransferase (AST, SGOT) ≤ 2.5 x ULN (≤ 5 x ULN if liver metastases are present); * INR ≤ 1.5 x ULN; * serum creatinine ≤ ULN or creatinine clearance ≥ 60 mL/min (by Cockcroft \& Gault formula or alternate calculation by 24hr urine collection). Patients with serum creatinine ≤ ULN and clearance between 45 to 59 mL/min should reduce cisplatin dose by 50%; * serum potassium ≥ 3.0 and ≤ 5.5 mmol/L; * serum calcium ≥ 8.0 and ≤ 11.5 mg/dL (≥ 2.0 and ≤ 2.9 mmol/L); * serum magnesium ≥ 1.2 and ≤ 3.0 mg/dL (≥ 0.5 and ≤ 1.23 mmol/L); 8. Female patients of child-bearing potential …

Enrollment public domain (ClinicalTrials.gov)

Enrollment: 36 participants (actual).